PROJECT SUMMARY This project investigates the utility of dorsomedial prefrontal cortex(DMFPC) repetitive transcranial magnetic stimulation (rTMS) in bingeing and purging in chronic, treatment- resistant bulimia nervosa(BN), and anorexia nervosa, binge-purging subtype(ANBN). rTMS uses powerful, focused magnetic field pulses to change activity in target brain regions. Published pilot work shows 57% of those treated with DMPFC rTMS for bingeing and purging experience both a >50% reduction in both bingeing and purging, and a wide variety of improvements in other domains, including mood, anxiety, and affective regulation. Response in terms of reduced bingeing and purging does not appear to be correlated to other comorbidity. Response is heavily correlated to pre-treatment fronto- striatal connectivity as measured by functional magnetic resonance imaging(frmi), where responders have a consistent pattern of poor connectivity initially compared to non- responders, which pattern normalizes over the course of treatment The aims of the proposed R61/33 phased trial are to 1) confirm target engagement and determine an optimal dosing paradigm(R61 phase); and 2) ensure that the results are not due to a placebo effect, determine the clinical effectiveness and duration of effect, and begin to examine the potential use of pre-treatment fMRI as a biomarker of treatment suitability(R33 phase). Subjects in the R61 arm will undergo 30 bilateral rTMS treatments accompanied by a suite of imaging, clinical, psychometric, and psychological test assessments, in two dosage regimens and a sham arm. In the R33 phase, the optimal dosing regimen will be used with a novel active/sham coil to administer 20 rTMS treatments in a triple blind design. Subjects will again be assessed as in the R61 phase. If successful, the study will provide evidence for the future development of rTMS as a novel, effective treatment for refractory BN and ANBP, and further information as to the neural mechanisms both of the illnesses and the mechanism of response to rTMS.